The proposed research is directed toward elucidation of protein nucleic acid interactions at the molecular level. The system chosen for detailed investigation is the lac repressor protein and its operator DNA. Initially, efforts will be devoted to the isolation of subunits of the lac repressor, in order to obtain a species of lower molecular weight suitable for physical studies. Repressor subunits will be characterized with respect to DNA-binding activity (by membrane filtration), inducer-binding activity (by equilibrium dialysis), and the ability to undergo a change in conformation upon binding of inducer. The biochemical and physical properties of the subunits will be compared to those of the tetramer. The conformational transition in repressor tetramer and subunits will be studied by ultracentrifugation and stopped-flow. If a conformational change is detected in repressor subunits, this transition will be investigated further by high resolution NMR.